A liquid chromatographic MS-compatible method was applied to the structural elucidation of Teicoplanin for identification CRS components. The method, previously developed by our group, involves the use of LiChrospher 100 RP-18 column with a mobile phase composed of ammonium formate 25 mM at pH 6.00 and acetonitrile (ACN). All the peaks with a 0.10% UV area, largely above the disregard limit of 0.15% as fixed by EMA, were considered and submitted to MS/MS fragmentation experiments. The study of MS/MS spectrum collected for Teicoplanin complex major component (namely A2-2 ) allowed to elucidate the fragmentation pathway and enabled the successful identity assignment of all the 42 detected species...

OBJECTIVES: Social integration (involvement with a diverse array of social ties) has been linked to positive outcomes including better physical health. Research has not investigated whether encounters with diverse social ties enhance individuals' daily behaviors. The objectives of this study were to assess whether social ties connect individuals to more diverse daily behaviors, physical activity, and nonsedentary time as well as more positive mood. METHOD: Older adults (aged 65+, n = 313) provided information about their 10 closest social ties...

Recently, the FDA and EMA issued warnings on the use of dolutegravir and darunavir/cobicistat for treatment of pregnant women living with HIV. It took 3 to 5 years to identify the risks associated with the use of these antiretroviral drugs, during which time pregnant women were exposed to these drugs in clinical care, outside of controlled clinical trial settings. Across all antiretroviral drugs, the interval between registration of new drugs and first data on pharmacokinetics and safety in pregnancy becoming available is around 6 years...

The farnesoid X receptor (FXR) belongs to the nuclear receptor family and is activated by bile acids. Multiple, chemically rather diverse, FXR agonists have been developed and several of these compounds are currently tested in clinical trials for NAFLD and cholestasis. Here, we investigated possible FXR-agonism or antagonism of existing FDA/EMA-approved drugs. By using our recently developed FRET-sensor, containing the ligand binding domain of FXR (FXR-LBD), 1280 FDA-approved drugs were screened for their ability to activate FXR in living cells using flow cytometry...

Direct-acting antivirals (DAA) have markedly improved the treatment of hepatitis C, with a series of DAA combinations available for treatment. A sensitive method by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous quantification of seven commonly used DAAs, daclatasvir (DAC), elbasvir (ELB), grazoprevir (GZR), ledipasvir (LDV), simeprevir (SIM), sofosbuvir (SOF), velpatasvir (VEL) and the primary analyte of interest of SOF (GS-331007) in EDTA plasma...

Lung cancer is the leading cause of cancer death worldwide with low response rates to conventional chemotherapy. New promising therapies have emerged based on programmed cell death protein 1 (PD-1) immunity checkpoint inhibitors (ICI), including anti-PD-1, such as nivolumab and pembrolizumab, or programmed death ligand 1 (PD-L1) inhibitors, such as atezolizumab, durvalumab, and avelumab. The prescription of pembrolizumab has been approved by FDA and EMA for advanced stages non-small cell lung carcinoma (NSCLC), restricted for first-line setting to patients whose tumor presents ≥50% of PD-L1 positive tumor cells (TC), and ≥1% for second-line and beyond, leading to consider PD-L1 assay as a companion diagnostic tool for pembrolizumab...

Objective: A recent, global, increase in the use of opioids including the prescribing, highly potent, fentanyl has been recorded. Due its current popularity and the potential lethal consequences of its intake, we aimed here at analyzing the fentanyl misuse, abuse, dependence and withdrawal-related adverse drug reactions (ADRs) identified within the European Medicines Agency (EMA), the United Kingdom Yellow Card Scheme (YCS), and the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) databases...

BACKGROUND: Conventional laparoscopic and open distal gastrectomy procedures have inherent limitations such as restricted movement of straight forceps and tremor of the tip of the devices that can potentially be overcome using robotic distal gastrectomy (RDG). This single-institutional phase II trial aimed to evaluate the safety and feasibility of RDG with lymph node dissection for clinical stage IA gastric cancer. METHODS: The study included patients with clinical stage IA gastric cancer in the lower two-thirds of the stomach considered to be curatively resected via distal gastrectomy...

Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a long elimination half-life, allowing subcutaneous (sc) administration once per week. Both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recently approved once-weekly sc semaglutide for the treatment of type 2 diabetes mellitus (T2DM). The weight loss efficacy of once-weekly sc semaglutide appears to be superior compared with the other once-weekly GLP-1 RAs in patients with T2DM. Semaglutide was recently evaluated as an antiobesity drug in a phase II dose-finding trial, which demonstrated superior weight loss efficacy of once daily sc semaglutide compared with both placebo and once daily 3...

The human epigenome plays a key role in determining cellular identity and eventually function. Drug discovery undertakings have focused mainly on the role of genomics in carcinogenesis, with the focus turning to the epigenome recently. Drugs targeting DNA and histone modifications are under development with some such as 5-azacytidine, decitabine, vorinostat, and panobinostat already approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This expert review offers a critical analysis of the epigenomics-guided drug discovery and development and the opportunities and challenges for the next decade...

Extragonadal primary yolk sac tumor of the intestinal tract origin is exceedingly rare. Through a multiple disciplinary team, the diagnosis and treatment of primary intestinal yolk sac tumor were further defined. We report 2 such cases with detailed histologic and immunohistochemical analysis. The two patients were a 7-year-old girl and a 29-year-old woman. Both of them preoperatively had an elevated serum alpha fetoprotein (AFP) level (≥ 1,210 ng/mL). The tumors are located in the intestine and imaging examination indicated the rectum as the primary site...

Hemisquaramide tweezers, a new family of H-bond donor organocatalysts, are reported. The catalysts could be synthesized within two steps. Among them, H8 -binaphthyl-linked hemisquaramide 7 markedly accelerated the synthesis of cyclic carbonates from epoxides and CO2 . The reactions proceeded well under mild and solvent-free conditions. Kinetic resolution was also achieved at -20 °C ( s = 3.0). The adjustable bite angle and orientation of the two NH groups of the catalysts are important for the high activity...

Nowadays, the infections of patients admitted to Intensive Care Units (ICUs) are one of the major public health problems; this is due to several factors, in primis an increase in antibiotic resistance and the inappropriate use of antibiotics. This editorial focuses on both new antibiotics approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the last decade (2010-2019), and on agents in advanced phase of development that have been developed, or are already approved, for the treatment of serious infections due to multidrug-resistant (MDR) bacteria, both Gram-positive (GPB) and Gram-negative (GNB) bacteria...

BACKGROUND: Flavored cigar sales have increased in recent years in the U.S. African American young adults (AAYAs) have high prevalence of smoking flavored cigars and dual use with cigarettes, but the predictors of use are unclear. We examined the predictors of flavored cigar smoking among AAYA dual users. METHODS: We analyzed data from an Ecological Momentary Assessment (EMA) study that captured near real-time affect, smoking cues, and tobacco smoking from eight text-messaging surveys per day over two weeks...

Guadecitabine (SGI-110), a dinucleotide of β‑decitabine and deoxyguanosine, is currently being evaluated in phase II/III clinical trials for the treatment of hematological malignancies and solid tumors. This article describes the development and validation of bioanalytical assays to quantify guadecitabine and its active metabolite β‑decitabine in human plasma, whole blood and urine using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Since β‑decitabine is rapidly metabolized further by cytidine deaminase, plasma and whole blood samples were kept on ice-water after collection and stabilized with tetrahydrouridine (THU) directly upon sample collection...

The current article critically reviews three methodological options for assessing drinking episodes in the natural environment. Ecological momentary assessment (EMA) typically involves using mobile devices to collect self-report data from participants in daily life. This technique is now widely used in alcohol research, but investigators have implemented diverse assessment strategies. This article focuses on 'high resolution' EMA protocols that oversample experiences and behaviors within individual drinking episodes...

Reliable results of pharmacokinetic and toxicokinetic studies are vital for correct decision making during drug discovery and development. Thus, ensuring high quality of bioanalytical methods is of critical importance. Incurred sample reanalysis (ISR)-one of the tools used to validate a method-is included in the bioanalytical regulatory recommendations. The methodology of this test is well established, but the estimation of the sample size is still commented on and contested. We have applied the hypergeometric distribution to evaluate ISR test passing rates in different clinical study sizes...

Introduction: Although cytological examination helps in diagnosis of malignancy in serous effusion, at times it is difficult to differentiate atypical reactive mesothelial cells from adenocarcinoma (AC) cells. To resolve this problem, various ancillary methods have been used. Immunocytochemistry (ICC) is one such commonly used technique in which various panel of antibodies has been tried. Unfortunately, so far no unique marker is available to solve this issue. Hence, the present study evaluates the efficacy of four antibody panel comprising of MOC-31, epithelial membrane antigen (EMA), calretinin (CAL), and mesothelin (MES) to solve this problem...

Building on established links between attachment insecurity and maladaptive emotion regulation, here we examine whether traitlike attachment style predicts individual differences in mothers' emotions in situations with and without their children. Using ecological momentary assessment (EMA), we measured the real-time positive and negative emotions of 145 mothers of young children across a 10-day period, with self-reported attachment and presence of children as predictors of individual differences in emotion...

Mind wandering is a commonly experienced phenomenon. Although self-report measures are available to assess these attentional lapses, examination of their correspondence with the reported frequency of these episodes in daily life is warranted. Using ecological momentary assessments (EMAs), the present study aimed to validate 3 mind-wandering measures: the Mind-Wandering Questionnaire (MWQ) and the Mind Wandering-Spontaneous (MW-S) and Mind Wandering-Deliberate (MW-D) measures in university students (N = 100)...